Periodontitis and Cognitive Decline in Alzheimer's Disease.

Mark Ide,Clive Holmes,Rachel Raybould,Paul Ibbett,Rebecca Sussams,James Fuller,Ursula Puenter,Rhodri Thomas,V Hugh Perry,David Culliford,Annette Stevens,Viv Hopkins,Marina Harris,Jessica Teeling,Pradeep Garg

doi:10.1371/journal.pone.0151081

Abstract

Periodontitis is common in the elderly and may become more common in Alzheimer’s disease because of a reduced ability to take care of oral hygiene as the disease progresses. Elevated antibodies to periodontal bacteria are associated with an increased systemic pro-inflammatory state. Elsewhere raised serum pro-inflammatory cytokines have been associated with an increased rate of cognitive decline in Alzheimer’s disease. We hypothesized that periodontitis would be associated with increased dementia severity and a more rapid cognitive decline in Alzheimer’s disease. We aimed to determine if periodontitis in Alzheimer’s disease is associated with both increased dementia severity and cognitive decline, and an increased systemic pro inflammatory state. In a six month observational cohort study 60 community dwelling participants with mild to moderate Alzheimer’s Disease were cognitively assessed and a blood sample taken for systemic inflammatory markers. Dental health was assessed by a dental hygienist, blind to cognitive outcomes. All assessments were repeated at six months. The presence of periodontitis at baseline was not related to baseline cognitive state but was associated with a six fold increase in the rate of cognitive decline as assessed by the ADAS-cog over a six month follow up period. Periodontitis at baseline was associated with a relative increase in the pro-inflammatory state over the six month follow up period. Our data showed that periodontitis is associated with an increase in cognitive decline in Alzheimer’s Disease, independent to baseline cognitive state, which may be mediated through effects on systemic inflammation.

Highlights

Periodontal disease is widespread in the UK population and typical of most other westernized countries including North America[1]
We hypothesised that periodontitis would increase with increasing dementia severity in Alzheimer’s Disease (AD) but that periodontitis would be associated with an increased rate of cognitive decline independent of the degree of dementia severity
No studies to date have examined whether, in a longitudinal study, poor dental health correlates with poorer cognitive outcomes that are independent to baseline cognitive state

Summary

Introduction

Periodontal disease is widespread in the UK population and typical of most other westernized countries including North America[1]. Periodontitis has been shown to be associated with a raised serum pro-inflammatory state as shown by increases in C Reactive Protein (CRP) [4] and pro-inflammatory cytokines (e.g. Tumour Necrosis Factor α (TNFα)) with a reduction in anti-inflammatory markers (e.g. interleukin 10 (IL 10)) [5]. In Alzheimer’s Disease (AD) periodontitis may be even more common because of a reduced ability to take care of oral hygiene as the disease progresses and in AD increased elevation of serum levels of antibodies with associated increases in TNFα have been reported [8]. We have previously shown that chronic inflammatory diseases are associated with increased systemic proinflammatory cytokines and an increased rate of cognitive decline in AD [9]. We further hypothesised that periodontitis would be associated with a relative increase in systemic measures of the pro-inflammatory state and a decrease in anti-inflammatory state

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